Jiang Puen, Zong Kezhen, Peng Dadi, Zhou Baoyong, Wu Zhongjun
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
BMC Pharmacol Toxicol. 2025 Mar 19;26(1):65. doi: 10.1186/s40360-025-00884-5.
Pancreatic cancer (PC) is a highly aggressive malignancy with limited treatment options. Although gemcitabine monotherapy (G treatment) has long been a standard treatment, combination therapies, such as gemcitabine with albumin-bound paclitaxel (AG treatment), have shown improved outcomes and were approved by the FDA for the PC. However, the AG treatment is also associated with increased adverse events (AEs), which remain inadequately evaluated in real-world settings.
We utilized the FDA Adverse Event Reporting System (FAERS) to conduct a large-scale pharmacovigilance analysis comparing the safety profiles of G and AG treatments for PC. By analyzing adverse event data from the third quarter of 2013 to the second quarter of 2024 and quantifying AE signals with reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods, we compared the risk of AEs between the groups. Time to onset (TTO), subgroup and logistic regression analyses were also performed.
The study revealed a higher proportion of male (n = 2307, 54.1%) and elderly patients (age ≥ 65years, n = 2172, 50.9%) in the AG treatment group compared to the G treatment group. We found 17 preferred terms with positive signals at the top 50 common AEs, especially in gastrointestinal and blood systems. Cardiac and neurological AEs also needed to be vigilant. Biliary sepsis and infectious enterocolitis were newly identified AEs and deserve attention. Median TTO was 34 (IQR: 8-103) days (G) and 41 (IQR: 10-104) days (AG), with most AEs occurring within the first month (48.3% and 44%). Subgroup analysis revealed that male patients using the AG treatment had the highest risk of immune-mediated hepatitis (ROR = 23.51, 95% CI = 3.21-172.1), while elderly patients had elevated risks for presyncope (ROR = 24.84, 95% CI = 3.40-181.28) and falls (ROR = 18.60, 95% CI = 2.53-136.97). Logistic regression showed higher-risk fatal outcomes in males (adjusted OR = 1.42, 95% CI = 1.15-1.76, P < 0.01) and elderly patients (adjusted OR = 1.36, 95% CI = 1.10-1.69, P < 0.01).
This research offers critical safety insights in real-world settings, emphasizing patients at heightened AEs risk and informing clinical decision-making in PC treatment.
胰腺癌（PC）是一种侵袭性很强的恶性肿瘤，治疗选择有限。尽管吉西他滨单药治疗（G治疗）长期以来一直是标准治疗方法，但联合疗法，如吉西他滨与白蛋白结合型紫杉醇联合治疗（AG治疗），已显示出更好的疗效，并获得美国食品药品监督管理局（FDA）批准用于治疗胰腺癌。然而，AG治疗也与不良事件（AE）增加有关，在现实环境中对其评估仍不充分。
我们利用FDA不良事件报告系统（FAERS）进行大规模药物警戒分析，比较G和AG治疗胰腺癌的安全性。通过分析2013年第三季度至2024年第二季度的不良事件数据，并用报告比值比（ROR）和比例报告比（PRR）方法量化AE信号，我们比较了两组之间AE的风险。还进行了发病时间（TTO）、亚组和逻辑回归分析。
研究发现，与G治疗组相比，AG治疗组男性患者（n = 2307，54.1%）和老年患者（年龄≥65岁，n = 2172，50.9%）的比例更高。我们在50种常见AE中发现了17个有阳性信号的首选术语，特别是在胃肠道和血液系统方面。心脏和神经系统AE也需要警惕。胆汁性败血症和感染性小肠结肠炎是新发现的AE，值得关注。中位TTO为34（四分位间距：8 - 103）天（G治疗）和41（四分位间距：10 - 104）天（AG治疗），大多数AE发生在第一个月内（48.3%和44%）。亚组分析显示，使用AG治疗的男性患者发生免疫介导性肝炎的风险最高（ROR = 23.51，95%置信区间 = 3.21 - 172.1），而老年患者发生晕厥前状态（ROR = 24.84，95%置信区间 = 3.40 - 181.28）和跌倒（ROR = 18.60，95%置信区间 = 2.53 - 136.•97）的风险升高。逻辑回归显示，男性（调整后OR = 1.42，95%置信区间 = 1.15 - 1.76，P < 0.01）和老年患者（调整后OR = 1.36，95%置信区间 = 1.10 - 1.69，P < 0.01）的致命结局风险更高。
本研究在现实环境中提供了关键的安全性见解，强调了AE风险较高的患者，并为胰腺癌治疗中的临床决策提供了参考。
